Objective: This study aimed to explore the adverse drug reactions (ADRs) reported by patients and to identify drug-drug interactions (DDIs) among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients. Subjects and Methods: This cross-sectional study was conducted at the Medication Therapy Adherence Clinic, Hospital Sungai Buloh, an HIV/AIDS referral centre. The patients were randomly selected and were encouraged to describe ADRs caused specifically by any of the prescribed antiretroviral drugs (ARDs). Sociodemographic characteristics were recorded from the patients' medical records. In addition data on antiretroviral treatment (ART), DDIs and other conventional medication were also documented. Results: A total of 325 randomly selected HIV/AIDS patients with a mean age of 22.94 years participated in the study. The most frequently prescribed ARDs were lamivudine (64.6%), zidovudine (40.6%) and efavirenz (42.5%). Commonly reported ADRs were fatigue (54.8%), allergic reactions (41.5%), weight loss (41.5%), dry mouth (35.1%) and memory loss (35.1%). Female (87.8%), non-complementary and alternative medicine (CAM) users (87.3%) and participants below 50 years old (81.1%) were identified as having a higher prevalence of ADRs compared to males (79.6%), CAM users (78.7%) and participants aged 50 years or more (77.5%). Patient age was found to be significantly associated (p = 0.048) with the ADRs. In addition, a total of 44 cases of DDIs belonging to category D were also found in this study. Conclusions: This study enabled us to identify the most common ADRs and DDIs associated with the use of ART. Safe and effective treatment depends on the healthcare providers' knowledge of the same.